P00636 (F16P1_PIG) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fructose-1,6-bisphosphatase 1
Short name=FBPase 1
EC=3.1.3.11

Alternative name(s):
D-fructose-1,6-bisphosphate 1-phosphohydrolase 1

Gene names

Name:	FBP1
Synonyms:	FBP

Organism

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	338 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	D-fructose 1,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.
Cofactor	Binds 3 magnesium ions per subunit. Ref.9 Ref.11 Ref.12 Ref.13
Enzyme regulation	Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects. Ref.6 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14
Pathway	Carbohydrate biosynthesis; gluconeogenesis.
Subunit structure	Homotetramer. Ref.6 Ref.10 Ref.12 Ref.13 Ref.14
Miscellaneous	The molecule has a highly reactive cysteine residue (Cys-117 or Cys-129), which tends to form mixed disulfides (e.g. with homocystine) but is not essential for enzyme activity.
Sequence similarities	Belongs to the FBPase class 1 family.
Biophysicochemical properties	Kinetic parameters: KM=1.2 µM for fructose-1,6-diphosphate Ref.13

Ontologies

Keywords
Biological process	Carbohydrate metabolism Gluconeogenesis
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to drug Inferred from sequence or structural similarity. Source: UniProtKB cellular response to magnesium ion Inferred from sequence or structural similarity. Source: UniProtKB fructose 6-phosphate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB gluconeogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of Ras protein signal transduction Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of glycolysis Inferred from sequence or structural similarity. Source: UniProtKB protein homotetramerization Inferred from sequence or structural similarity. Source: UniProtKB regulation of gluconeogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	AMP binding Inferred from sequence or structural similarity. Source: UniProtKB fructose 1,6-bisphosphate 1-phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from sequence or structural similarity. Source: UniProtKB monosaccharide binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2 Ref.3

Chain

2 – 338

337

Fructose-1,6-bisphosphatase 1

PRO_0000200500

Regions

Nucleotide binding

18 – 22

5

AMP

Nucleotide binding

28 – 32

5

AMP

Nucleotide binding

113 – 114

2

AMP

Region

122 – 125

4

Substrate binding

Region

213 – 216

4

Substrate binding

Region

244 – 249

6

Substrate binding

Region

275 – 277

3

Substrate binding

Sites

Metal binding

69

1

Magnesium 1

Metal binding

98

1

Magnesium 1

Metal binding

98

1

Magnesium 2

Metal binding

119

1

Magnesium 2

Metal binding

119

1

Magnesium 3

Metal binding

121

1

Magnesium 2; via carbonyl oxygen

Metal binding

122

1

Magnesium 3

Metal binding

281

1

Magnesium 3

Binding site

141

1

AMP

Binding site

265

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylthreonine Ref.2 Ref.3

Modified residue

208

1

Phosphoserine; by PKA Ref.2

Experimental info

Mutagenesis

55

1

A → L: Destabilizes the inactive T-state and promotes transition to the R-state.

Sequence conflict

2

1

T → A AA sequence Ref.3

Sequence conflict

4

1

Q → E AA sequence Ref.3

Sequence conflict

21

1

E → Q AA sequence Ref.2

Sequence conflict

97

1

S → T AA sequence Ref.2

Sequence conflict

157

1

G → E AA sequence Ref.2

Sequence conflict

200

1

D → N AA sequence Ref.2

Sequence conflict

229

1

Q → E AA sequence Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

338

Helix Strand Turn

Details...

Helix

14 – 24

11

Helix

30 – 50

21

Turn

51 – 56

6

Beta strand

59 – 64

6

Beta strand

66 – 68

3

Beta strand

70 – 72

3

Helix

73 – 88

16

Beta strand

92 – 97

6

Beta strand

101 – 105

5

Helix

108 – 110

3

Beta strand

111 – 122

12

Helix

124 – 126

3

Turn

127 – 130

4

Beta strand

133 – 141

9

Beta strand

144 – 146

3

Beta strand

147 – 149

3

Helix

150 – 153

4

Helix

157 – 159

3

Beta strand

161 – 178

18

Beta strand

181 – 188

8

Turn

189 – 192

4

Beta strand

193 – 198

6

Beta strand

208 – 211

4

Helix

214 – 219

6

Helix

222 – 232

11

Beta strand

235 – 237

3

Beta strand

242 – 245

4

Helix

249 – 259

11

Beta strand

262 – 265

4

Beta strand

268 – 270

3

Turn

271 – 273

3

Beta strand

275 – 277

3

Turn

278 – 281

4

Helix

282 – 291

10

Beta strand

295 – 297

3

Beta strand

299 – 302

4

Helix

303 – 305

3

Beta strand

309 – 312

4

Beta strand

317 – 320

4

Helix

322 – 334

13

Sequences

	Sequence		Length	Mass (Da)
	P00636 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 610BF8D3C6D320F6	FASTA	338	36,779
	10 20 30 40 50 60 MTDQAAFDTN IVTLTRFVME EGRKARGTGE MTQLLNSLCT AVKAISTAVR KAGIAHLYGI 70 80 90 100 110 120 AGSTNVTGDQ VKKLDVLSND LVINVLKSSF ATCVLVSEED KNAIIVEPEK RGKYVVCFDP 130 140 150 160 170 180 LDGSSNIDCL VSIGTIFGIY RKNSTDEPSE KDALQPGRNL VAAGYALYGS ATMLVLAMVN 190 200 210 220 230 240 GVNCFMLDPA IGEFILVDRD VKIKKKGSIY SINEGYAKEF DPAITEYIQR KKFPPDNSAP 250 260 270 280 290 300 YGARYVGSMV ADVHRTLVYG GIFMYPANKK SPKGKLRLLY ECNPMAYVME KAGGLATTGK 310 320 330 EAVLDIVPTD IHQRAPIILG SPEDVTELLE IYQKHAAK

References

[1]	"Isolation and sequence analysis of the cDNA for pig kidney fructose 1,6-bisphosphatase." Williams M.K., Kantrowitz E.R. Proc. Natl. Acad. Sci. U.S.A. 89:3080-3082(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Complete amino acid sequence of pig kidney fructose-1,6-bisphosphatase." Marcus F., Edelstein I., Reardon I., Heinrikson R.L. Proc. Natl. Acad. Sci. U.S.A. 79:7161-7165(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-336, ACETYLATION AT THR-2, PHOSPHORYLATION AT SER-208. Tissue: Kidney cortex.
[3]	"Conservation of primary structure at the proteinase-sensitive site of fructose 1,6-bisphosphatases." McGregor J.S., Hannappel E., Xu G.-J., Pontremoli S., Horecker B.L. Arch. Biochem. Biophys. 217:652-664(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-24 AND 44-61, ACETYLATION AT THR-2. Tissue: Kidney.
[4]	"Mechanism of action of fructose 1,6-bisphosphatase." Benkovic S.J., Demaine M.M. Adv. Enzymol. Relat. Areas Mol. Biol. 53:45-82(1982) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE-BINDING SITE, LIGANDS, REVIEW.
[5]	"Structure refinement of fructose-1,6-bisphosphatase and its fructose 2,6-bisphosphate complex at 2.8-A resolution." Ke H.M., Thorpe C.M., Seaton B.A., Lipscomb W.N., Marcus F. J. Mol. Biol. 212:513-539(1990) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-2,6-BISPHOSPHATE, SEQUENCE REVISION.
[6]	"Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 6-phosphate, AMP, and magnesium." Ke H.M., Zhang Y.P., Lipscomb W.N. Proc. Natl. Acad. Sci. U.S.A. 87:5243-5247(1990) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-6-PHOSPHATE; AMP AND MAGNESIUM, ENZYME REGULATION, SUBUNIT.
[7]	"Crystal structure of the neutral form of fructose-1,6-bisphosphatase complexed with the product fructose 6-phosphate at 2.1-A resolution." Ke H.M., Zhang Y.P., Liang J.-Y., Lipscomb W.N. Proc. Natl. Acad. Sci. U.S.A. 88:2989-2993(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-6-PHOSPHATE.
[8]	"Crystal structure of the neutral form of fructose 1,6-bisphosphatase complexed with regulatory inhibitor fructose 2,6-bisphosphate at 2.6-A resolution." Liang J.-Y., Huang S., Zhang Y.P., Ke H.M., Lipscomb W.N. Proc. Natl. Acad. Sci. U.S.A. 89:2404-2408(1992) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-2,6-BISPHOSPHATE.
[9]	"Role of a dynamic loop in cation activation and allosteric regulation of recombinant porcine fructose-1,6-bisphosphatase." Choe J.-Y., Poland B.W., Fromm H.J., Honzatko R.B. Biochemistry 37:11441-11450(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) IN COMPLEX WITH ZINC IONS, COFACTOR, ENZYME REGULATION.
[10]	"Crystal structures of fructose 1,6-bisphosphatase: mechanism of catalysis and allosteric inhibition revealed in product complexes." Choe J.-Y., Fromm H.J., Honzatko R.B. Biochemistry 39:8565-8574(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) IN COMPLEXES WITH FRUCTOSE-6-PHOSPHATE; PHOSPHATE; AMP; MAGNESIUM AND ZINC IONS, SUBUNIT, ENZYME REGULATION.
[11]	"Metaphosphate in the active site of fructose-1,6-bisphosphatase." Choe J.-Y., Iancu C.V., Fromm H.J., Honzatko R.B. J. Biol. Chem. 278:16015-16020(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM IONS; FRUCTOSE-6-PHOSPHATE AND PHOSPHATE, COFACTOR, ENZYME MECHANISM.
[12]	"Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors." Choe J.-Y., Nelson S.W., Arienti K.L., Axe F.U., Collins T.L., Jones T.K., Kimmich R.D.A., Newman M.J., Norvell K., Ripka W.C., Romano S.J., Short K.M., Slee D.H., Fromm H.J., Honzatko R.B. J. Biol. Chem. 278:51176-51183(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH THE SYNTHETIC INHIBITOR OC252; FRUCTOSE-6-PHOSPHATE; PHOSPHATE AND DIVALENT METAL CATIONS, COFACTOR, SUBUNIT, ENZYME REGULATION.
[13]	"R-state AMP complex reveals initial steps of the quaternary transition of fructose-1,6-bisphosphatase." Iancu C.V., Mukund S., Fromm H.J., Honzatko R.B. J. Biol. Chem. 280:19737-19745(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF MUTANT LEU-55 IN COMPLEXES WITH AMP; FRUCTORSE-6-PHOSPHAT; PHOSPHATE AND MAGNESIUM IONS, SUBUNIT, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[14]	"Structures of mammalian and bacterial fructose-1,6-bisphosphatase reveal the basis for synergism in AMP/fructose 2,6-bisphosphate inhibition." Hines J.K., Chen X., Nix J.C., Fromm H.J., Honzatko R.B. J. Biol. Chem. 282:36121-36131(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM IONS AND FRUCTOSE-2,6-DIPHOSPHATE, SUBUNIT, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M86347 mRNA. Translation: AAA31035.1.

PIR

PAPGF. S37696.

RefSeq

NP_999144.1. NM_213979.1.

UniGene

Ssc.5127.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CNQ	X-ray	2.27	A	2-338	[»]
1EYI	X-ray	2.32	A	2-338	[»]
1EYJ	X-ray	2.28	A/B	2-338	[»]
1EYK	X-ray	2.23	A/B	2-338	[»]
1FBC	X-ray	2.60	A/B	2-336	[»]
1FBD	X-ray	2.90	A/B	2-336	[»]
1FBE	X-ray	3.00	A/B	2-336	[»]
1FBF	X-ray	2.70	A/B	2-336	[»]
1FBG	X-ray	3.00	A/B	2-336	[»]
1FBH	X-ray	2.50	A/B	2-336	[»]
1FBP	X-ray	2.50	A/B	2-336	[»]
1FJ6	X-ray	2.50	A	2-338	[»]
1FJ9	X-ray	2.50	A/B	2-338	[»]
1FPB	X-ray	2.60	A/B	2-336	[»]
1FPD	X-ray	2.10	A/B	2-336	[»]
1FPE	X-ray	2.20	A/B	2-336	[»]
1FPF	X-ray	2.10	A/B	2-336	[»]
1FPG	X-ray	2.30	A/B	2-336	[»]
1FPI	X-ray	2.30	A/B	2-336	[»]
1FPJ	X-ray	2.20	A/B	2-336	[»]
1FPK	X-ray	3.00	A/B	2-336	[»]
1FPL	X-ray	2.30	A/B	2-336	[»]
1FRP	X-ray	2.00	A/B	2-336	[»]
1FSA	X-ray	2.30	A/B	2-338	[»]
1KZ8	X-ray	2.00	A/F	2-338	[»]
1LEV	X-ray	2.15	A/F	2-338	[»]
1NUW	X-ray	1.30	A	2-338	[»]
1NUX	X-ray	1.60	A	2-338	[»]
1NUY	X-ray	1.30	A	2-338	[»]
1NUZ	X-ray	1.90	A	2-338	[»]
1NV0	X-ray	1.80	A	2-338	[»]
1NV1	X-ray	1.90	A	2-338	[»]
1NV2	X-ray	2.10	A	2-338	[»]
1NV3	X-ray	2.00	A	2-338	[»]
1NV4	X-ray	1.90	A	2-338	[»]
1NV5	X-ray	1.90	A	2-338	[»]
1NV6	X-ray	2.15	A	2-338	[»]
1NV7	X-ray	2.15	A/B	1-338	[»]
1Q9D	X-ray	2.35	A/B	2-338	[»]
1RDX	X-ray	2.75	A/B	2-338	[»]
1RDY	X-ray	2.20	A/B	2-338	[»]
1RDZ	X-ray	2.05	A/B	2-338	[»]
1YXI	X-ray	2.00	A	2-338	[»]
1YYZ	X-ray	1.85	A	2-338	[»]
1YZ0	X-ray	2.07	A/B	2-338	[»]
2F3B	X-ray	1.80	A	2-338	[»]
2F3D	X-ray	1.83	A	2-338	[»]
2F3H	X-ray	2.70	A/B	2-338	[»]
2FBP	X-ray	2.80	A/B	2-336	[»]
2QVU	X-ray	1.50	A/B	2-338	[»]
2QVV	X-ray	2.03	A/B	2-338	[»]
3FBP	X-ray	2.80	A/B	2-336	[»]
4FBP	X-ray	2.50	A/B/C/D	2-336	[»]
5FBP	X-ray	2.10	A/B	2-336	[»]

ProteinModelPortal

P00636.

SMR

P00636. Positions 7-338.

ModBase

Search...

Proteomic databases

PaxDb

P00636.

PRIDE

P00636.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

397038.

KEGG

ssc:397038.

Organism-specific databases

CTD

2203.

Phylogenomic databases

eggNOG

COG0158.

HOGENOM

HOG000191265.

HOVERGEN

HBG005627.

KO

K03841.

OrthoDB

EOG4P8FJF.

Enzyme and pathway databases

BRENDA

3.1.3.11. 6170.

SABIO-RK

P00636.

UniPathway

UPA00138.

Family and domain databases

InterPro

IPR000146. FBPase_class-1/SBPase.
IPR020548. Fructose_bisphosphatase_AS.
[Graphical view]

PANTHER

PTHR11556. PTHR11556. 1 hit.

Pfam

PF00316. FBPase. 1 hit.
[Graphical view]

PIRSF

PIRSF000904. FBPtase_SBPase. 1 hit.

PRINTS

PR00115. F16BPHPHTASE.

PROSITE

PS00124. FBPASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00636.

ChEMBL

CHEMBL2263.

DrugBank

DB00131. Adenosine monophosphate.

EvolutionaryTrace

P00636.

Entry information

Entry name

F16P1_PIG

Accession

Primary (citable) accession number: P00636

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program